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Biomaterials. 2015 Aug;61:103-14. doi: 10.1016/j.biomaterials.2015.04.057. Epub 2015 May 19.

Tissue engineered humanized bone supports human hematopoiesis in vivo.

Author information

1
Regenerative Medicine Group, Institute of Health and Biomedical Innovation, Queensland University of Technology, 60 Musk Avenue, Kelvin Grove, QLD 4049, Brisbane, Australia; Orthopedic Center for Musculoskeletal Research, University of Wuerzburg, Koenig-Ludwig-Haus, Brettreichstr. 11, 97074 Wuerzburg, Germany.
2
Regenerative Medicine Group, Institute of Health and Biomedical Innovation, Queensland University of Technology, 60 Musk Avenue, Kelvin Grove, QLD 4049, Brisbane, Australia; George W Woodruff School of Mechanical Engineering, Georgia Institute of Technology, 801 Ferst Drive Northwest, Atlanta, GA 30332, USA; Institute for Advanced Study, Technical University Munich, Lichtenbergstraße 2a, 85748 Garching, Munich, Germany. Electronic address: dietmar.hutmacher@qut.edu.au.
3
Stem Cell Biology Group and Stem Cells and Cancer Group - Blood and Bone Diseases Program, Mater Research Institute - The University of Queensland, Translational Research Institute, 37 Kent Street, Woolloongabba, QLD 4102, Brisbane, Australia.
4
Regenerative Medicine Group, Institute of Health and Biomedical Innovation, Queensland University of Technology, 60 Musk Avenue, Kelvin Grove, QLD 4049, Brisbane, Australia.
5
Australian Prostate Cancer Research Centre Queensland, Translational Research Institute, 37 Kent Street, Woolloongabba, QLD 4102, Brisbane, Australia.
6
Australian Prostate Cancer Research Centre Queensland, Translational Research Institute, 37 Kent Street, Woolloongabba, QLD 4102, Brisbane, Australia; Cells and Tissue Domain, Institute of Health and Biomedical Innovation, Queensland University of Technology, 60 Musk Avenue, Kelvin Grove, QLD 4049, Brisbane, Australia.
7
Bones and Immunology Group - Blood and Bone Diseases Program, Mater Research Institute - The University of Queensland, Translational Research Institute, 37 Kent Street, Woolloongabba, QLD 4102, Brisbane, Australia.
8
Stem Cell Biology Group and Stem Cells and Cancer Group - Blood and Bone Diseases Program, Mater Research Institute - The University of Queensland, Translational Research Institute, 37 Kent Street, Woolloongabba, QLD 4102, Brisbane, Australia; School of Medicine, The University of Queensland, 288 Herston Road, Herston, QLD 4006, Brisbane, Australia. Electronic address: jp.levesque@mater.uq.edu.au.

Abstract

Advances in tissue-engineering have resulted in a versatile tool-box to specifically design a tailored microenvironment for hematopoietic stem cells (HSCs) in order to study diseases that develop within this setting. However, most current in vivo models fail to recapitulate the biological processes seen in humans. Here we describe a highly reproducible method to engineer humanized bone constructs that are able to recapitulate the morphological features and biological functions of the HSC niches. Ectopic implantation of biodegradable composite scaffolds cultured for 4 weeks with human mesenchymal progenitor cells and loaded with rhBMP-7 resulted in the development of a chimeric bone organ including a large number of human mesenchymal cells which were shown to be metabolically active and capable of establishing a humanized microenvironment supportive of the homing and maintenance of human HSCs. A syngeneic mouse-to-mouse transplantation assay was used to prove the functionality of the tissue-engineered ossicles. We predict that the ability to tissue engineer a morphologically intact and functional large-volume bone organ with a humanized bone marrow compartment will help to further elucidate physiological or pathological interactions between human HSCs and their native niches.

KEYWORDS:

Bone organ; Engraftment; Hematopoietic stem cells; Humanized niche; Tissue Engineering; Transplantation

[Indexed for MEDLINE]

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